Quinine

Powdered dried bark of the cinchona tree,

a native of South America, was made into
a drink and used by the Quechua Indians
of Peru to treat fevers.
Discovered by Jesuit priests in the
1620s, Barnab de Cobo takes cinchona
bark to Europe in 1632 to treat malaria.
Quinine isolated in
1820 by Pierre Joseph
Pelletier and Joseph
Caventou

First Total Synthesis

(1943) RB Woodward
and WE von Doering

Synthesis of Chloroquine
using the Conrad-Limpach quinolone method

Papaverine
Papaverine is an opium alkaloid found in the
opium poppy, but papaverine differs in both
structure and pharmacological action from the
other opium alkaloids.

Paperverine is a smooth muscle relaxant. It belongs to the group of

medicines called vasodilators.
Vasodilators cause blood vessels to expand, thereby increasing
blood flow, and are used to treat problems resulting from poor blood
circulation.

Synthesis of Papaverine
using the Pictet Gams modification of the Bischler-Naperialski method

Indomethacin
Indomethacin is a non-steroidal anti-inflammatory
drug (NSAID) discovered in 1963

Indomethacin is a non-selective inhibitor of

cyclooxygenase 1 and 2 (COX1 and COX2),
enzymes that participate in biosynthesis of
prostaglandins from arachidonic acid.
Prostaglandins are hormone-like molecules
which have a wide variety of effects, some of
which lead to pain, fever, and inflammation.
Prostaglandin E1 (PGE1)

Synthesis of Indomethacin
using the Fischer indole synthesis

Spirooxazines
Photochromic materials change colour upon the action of UV light or
direct sunlight. A structural change alters the conjugation in the
molecule and thus the absorption of the molecule in the visible part of
the electromagnetic spectrum.
In this example the
spiro system twists
from a perpendicular
(closed) form to a
flat, planar (opened)
structure via an
electrocyclic ring
opening reaction.
This allows the two halves to become conjugated, resulting in the
absorption of visible light and a change from colourless to coloured

Synthesis of spirooxazines
Fischer indole followed by
an aldol-like condensation
and cyclization

Galanthamine
Galanthamine is isolated
from the common snowdrop
(Galanthus nivalis).

Galanthamine inhibits acetylcholine esterase (AChE) which is

a key enzyme involved in the transmission of nerve impulses.

It has been approved for use as a treatment for Alzheimer's disease.

Synthesis of Galanthamine

 Secretase Inhibitors
Alzheimers disease (AD) is a progressive and chronic neurodegenerative
disease that leads to loss of intellect and memory.
A pathological characteristic of this disease the production of the 40-42
residue peptide amyloid- (A). The protease enzyme -secretase plays a
critical role through cleavage of the -amyloid precursor protein (APP).
Plaques, made of aggregates of the A peptide, can
form in the brains of AD patients. -Secretase is a
potential target for AD therapeutic intervention.

Merck lead compound

Inhibitor Synthesis

Cocaine
Cocaine is a crystalline tropane
alkaloid that is obtained from
the leaves of the coca plant.

It is a stimulant of the central nervous system and an appetite

suppressant, creating what has been described as a euphoric sense of
happiness and increased energy.
Cocaine is also a topical anaesthetic
used in eye, throat, and nose surgery
The pharmacodynamics of cocaine
are complex.

Synthesis of Cocaine

Further Information
The references below relate to the synthetic methods presented
only. General information about the compounds and their
applications can be found on the web and in the library.
Chloroquine: J. Am. Chem Soc., 1946, 68, 113-116.
Papaverine: J. Org. Chem., 1981, 46, 3742-3745 and Chem. Ber.,
1909, 42 2951.
Indomethacin: J. Am. Chem Soc., 1955, 77, 4319-4324 and J. Am.
Chem Soc., 1963, 85, 488-489.
Photochromics: see, for one example of many, J. Heterocycl. Chem.,
2004, 41, 103-108 (synthesis of indolium salt) and J. Heterocycl.
Chem., 2002, 39, 179-184 (synthesis of spirooxazine).
Galanthamine: Angew. Chem., Int. Ed. Engl., 2001, 40, 3060.
-Secretase inhibitor: J. Org. Chem. 2006, 71, 3086-3092.
Cocaine: Tetrahedron Lett., 1978,1733-1736.